Why 11-beta-hydroxylase deficiency causes hypertension even though it results in reduced aldosterone synthesis:

" because of overproduction of cortisol precursors that are, or are metabolized to, mineralocorticoid agonists." Source

primary Syphilia:

• After an incubation period of 3 to 4 weeks (range 1 to 13 weeks), a primary lesion (chancre) develops at the site of inoculation. The initial red papule quickly forms a chancre
• The chancre usually heals in 3 to 12 weeks.

Secondary syphilis

• Cutaneous T cell lymphoma - usually limited to the skin. Looks like pityriasys versicolor.
• benign course
• Phototherapy is a treatment.
• Looks eczematous or like psoriasis; often initially on buttocks.
  

[!INFO] Mnemonics
REDMAN or SCALP-ID
REDMAN : Eczema / psoriasis, Drugs, Malignancy (mycosis fungoides, CTCL, Autoimmune, No identifiable cause)

SCALP-ID

• Either sporadic or #autosomalDominant

• Normally, the kidney deactivates cortisol via the enzyme 11-beta-dehydrogenase isozyme 2 to inactive cortisone, thus 'protecting' it's mineralocorticoid receptors from the effects of cortisol. Source
• In ectopic ACTH mediated Cushing's syndrome, this inactivation is overwhelmed and cortisol acts on the aldosterone receptors -> producing hypokalemia.
• #2021GM-JUL/Q16 Deficiency of 11-beta-dehydrogenase occurs in "apparent mineralocorticoid excess".
  #2021GM-JUL/Q16

Apparent mineralocorticoid excess syndrome

[!TIP] Mnemonic: Similar to Conn's syndrome but with low renin and aldosterone.

Caused by deficiency of 11-beta-dehydrogenase.
Features:

• Hypokalemia

• Metabolic alkalosis

• Low plasma renin activity

• Low plasma aldosterone levels

• Chronic liquorice (licorice) ingestion causes a similar picture. It inhibits 11-beta-dehydrogenase.

Organism excreted via urine of infected animal. (Only a minority of humans excrete organisms in urine - that's from second week onwards)

• Most symptomatic patients have anicteric disease.
  • Anicteric disease has only flu like symptoms. (headache, fever, myalgia, cough, anorexia, diarrhoea etc) and it self limiting. Source
• Conjunctival suffusion is an important sign - minority have a sub conjunctival haemorrhage; but suffusion is the commoner manifestation.
  Leptospiraemic phase = septicaemic phase.
  Blood and CSF culture won't be positive in the immune phase.

Usually non-oliguric and hypokalemic.

• Pulsed steroid therapy can be given for severe disease (esp. pulmonary involvement) (methylprednisolone)

⭐Definition of AIDS :

• a CD4 cell count <200 cells/microL or
  :read the aids defining illnesses table:

• progressive, multifocal, subacute focal neurological deficits that vary depending on the site of the lesion and include a spectrum of presentations including cognitive impairment, limb ataxia, gait ataxia, hemiparesis, ⭐hemianopia, and aphasia.
• Optic nerve and Spinal cord are usually spared.
• T lymphocytes play a major role in the normal immune response to JC virus.
• PML is rare but fatal is most cases.
• JC is a DNA virus.

• Transmitted via larval tick bite. (trombiculid mites)

• Pathogen: Bacterium - Orientia tsutsugamushi : Obligate intracellular pathogen, belongs to ricketsia.

• Elderly can have CNS symptoms on presentation - sensoryneural hearing impairment.
  Eschar biopsy

• Eschar biopsy: lymphohistiocytic vasculitis.

• Immunofluorescense assay (IFA) - ⭐Gold standard but expensive. #immunofluorescence #goldStandard

Streptococci

Comparison of some medically important streptococci

[!TIP] Common terminology

• Pyogenes = GABS, Group B strep - Agalatiae; Pneumococcus = Strep pneumonia.

• Scarlet fever (not a late complication but a manifestation of infection)

• [[Nephrology miscellaneous#Membranoproliferative glomerulonephritis|Membranoproliferative(aka mesangioproliferative,aka mesangiocapillary) glomerulonephritis]]

[!INFO] Membranoproliferative and Mesangioproliferative are described under "acute nephritic syndromes" in Harrison's
This probably means they present more often as nephritic syndromes but also can have some proteinuria.

• Type 1: subendothelial immune complex deposition (or interposition of mesangial cells in the subendothelial space) -> splitting of capillary basement membrane -> tramline appearance. (Mnemonic: "All aboard the proliferative train") -> Tramlines
  • Type 1 MPGN is commonly associated with chronic hepatitis C infection
  • Nephrotic range proteinuria is a poor prognostic marker.
  • 
  • linear intramembranous-membranous deposits
    Causes of membranoproliferative glomerulonephritis

1. Autoimmune
2. Chronic infections

There is (From Harrison's)

1. Mesangial expansion +/- mesangial hypercellularity.
2. Single contoured capillary walls
3. Mesangial immune deposits.

• Presents with varying degrees of proteinuria and commonly haematuria.
  • Isolated haematuria -> very benign course;
    proteinuria + -> increased risk of renal failure.
• Most cases are caused by [[#IgA nephropathy]].
• Falciparum malaria is a cause.

C3 glomerulopathies

• Two types: Dense deposit disease (DDD) and C3 glomerulpathy. (C3GN)
• Defined by C3 mediated glomerulonephritis with no immunoglobulin involvement.
• C3 levels are low with normal C4 levels.
• The histological patterns of C3 glomerulopathies is most commonly membranoproliferative or mesangioproliferative.

• Autoimmune pancreatitis Type I (the commonest type) is seen in men. IgG4 positive with dense lymphoplasmacytic infiltrate.
  • Autoimmune pancreatitis responds well to steroids and lack of response should arouse suspicion of another diagnosis.
  • occurs independantly of trypsin activation.
• Autoimmune pancreatitis type II:
  • Main presenting feature is extrapancreatic symptoms.
  • Obstruction occurs early.
• Smoking is a risk factor -> smoking cessation is recommended in management.
• Pain: NSAIDS, tramadol, coeliac nerve block, TCA antidepressants for chronic pain, pregabalin.
• Steatorrhoea: usually occurs with long standing chronic pancreatitis. Enzyme supplements are given.
  • note that inadequate pancreatic bicarbonate secretion also contributes by ?inhibiting enzyme activation in the duodenum
  • Fat intake should NOT be reduced - will only worsen malnutrition.
• AKA type 3c diabeties or pancreatogenic diabetes.
• Occurs after many years of disease progression. (usually after the development of exocrine failure and malabsorption)
• A type of 'brittle' diabetes : patients have insulin deficiency (but rare ketosis) and also glucagon deficiency so they develop hypoglycaemia very easily while on treatment.
  • Counts within 150,000 to 100,000 range are likely to be [[#⭐Incidental thrombocytopaenia of pregnancy]].
• Defined as platelets < 150,000.
• There can be many causes. Commonest is incidental thrombocytopaenia of pregnancy.
• 75% - the cause is idiopathic and with mild thrombocytopaenia. - This is [[#⭐Incidental thrombocytopaenia of pregnancy]]
  • 21% - secondary to hypertensive disorder
  • 4% - immune thrombocytopaenic purpura.

⭐Incidental thrombocytopaenia of pregnancy

• Caused by haemodilution, among other causes.
• No treatment needed.
• creatine kinase, aminotransferases, LDH and aldolase are all raised.
  • Anti-Jo is more commonly seen in polymyositis than dermatomyositis.
  • Mnemonic: Jolly Polly

The surprising ones are highlighted; basically, myopathies tend to cause proximal symmetrical weakness; distal weakness is more likely due to nerve issues.

Paraneoplastic Dermatoses

Source

These are the Dermatoses which almost always occur with a malignancy.
| Lesion | Association | Mnemonic |
| ------------------------------------ | ----------------------------------------------------------- | ----------------------------------------------------------------------------- |
| Tripe palm (aka pachydermatoglyphia) | Lung cancer, gastric cancer | Occurs together with ANM |
| Acanthosis nigricans Maligna (ANM) | Gastric Adenocarcinoma | AN is connected to things relating to fat / stomach / tummy |
| Erythema gyratum repens | pulmonary, oesophageal, breast | Forests (wood grain appearance of rash) are the lungs of the world |
| Acquired hypertrichosis lanuginosa | colorectal, pulmonary and breast | Hairy butt |
| Bazex syndrome | Aerodigestive | |
| Acquired ichthyosis | Lymphoma | Lymfishma |
| Dermatomyositis | Ovarian Ca, Lung CA | Common in women -> ovaries.
Also, lungs
Associated with "paired organs" |
| Migratory thrombophlebitis | Pancreatic CA | Let's assume scorpion stings also case thrombosis |
| Necrolytic migratory erythema | Glucagonoma | Always carry glucose while migrating |
| Pyoderma gangrenosum | myeloproliferative disorders | pyo/myo |
| Sweet syndrome | Haematologic malignancies | Sweets raise blood sugar |
| Tylosis | Oesophageal cancer | Tie a tie around the oesophagus |
| Leser-Trelat | Gastric and colorectal | |
| Paraneoplastic pemphigus | NHL, CLL, Castleman Disease, Thymoma | |
| Pytiriasis rotunda | Hepatocellular carcinoma, gastric and oesophageal carcinoma | |
| Palmoplantar keratoderma | Oeseophageal SQC | |
| Pyoderma gangrenosum | | |
| Sweet syndrome | AML, MDS, | |
| pyoderma gangrenosum | MDS, myeloma, leukemia | |
Bazex syndrome

Pytiriasis rotunda

Necrolytic Migratory Erythema

Type 1 = H+ secretion defect in DCT.

Basis is hyperkeratosis and epidermal papillomatosis as seen on histology. Black color is not due to melanin but due to the hyperkaratosis. Source

Endocrine (Cushing's and Acromegaly)
N if for iNjected Insulin and other drugs

aka acute febrile neutrophilic dermatosis.

• Dermal neutrophilic infiltration
• Peripheral neutrophilia.
• Paraneoplastic manifestation of AML and MDS
  The old name was primary biliary cirrhosis.

• Most often diagnosed through routine screening.
• Usually asymptomatic.
• But Fatigue is a prominent presenting symptom. Pruritus is an early and common sign. Icterus is a late sign.

• There is destruction of small interlobular bile ducts.
• ⭐Antimitochondrial antibodies are found in all patients.
  • M2 is specific for PBC. (M2 is against the E2 subunit of pyruvate dehydrogenase complex)
• Presentation: ⭐Asymptomatic with #hepatomegaly and raised ALP. (raised ALP is often the only abnormal investigation)
• Histology:
  • portal tract infiltrate with hepatic granulomas; changes start in zone 1.
  4. Lungs - interstitial lung disease; upper and small airway involvement; Patients have ❗cough and dyspnoea.
  5. Other autoimmine diseases
• Keratoconjuntivis sicca - term for the occular manifestations of Sjogrens.
• Mikulicz syndrome: Parotid and lacrimal gland enlargement;
  • Characterized by sudden onset dry mouth leading to difficulty in swallowing.
  • Hard painless swellings of the salivary glands.
  • Symptoms are very similar to Sjogren's syndrome.
  • Sjogren's disease is one possible cause of this.
• Biopsy showing focal lymphocytic infitrate of labial salivary glands. Termed Focal lymphocytic sialadenitis.
• Anti Ro/SSA and anti La / SSB positivity suggests Sojgren's disease.
• "Amyloid" was meant to describe the starch like properties of the substance. Initially described as "waxy" and "lardaceous".
• Proteins which are normally soluble start getting deposited extracellularly as beta pleted fibrils.
  The four most common causes of systemic amyloid deposition are

(Both (AL and AA) have the beta pleted sheet structure) (Harrison's - page 804)

• Histological : Fat pad biopsy (less risk of bleeding)
• Organ biopsy is needed if a specific organ is involved.
• When Congo red stains binds to amyloid protein, it produces apple green birefringence.
• Looks similar to DM nephropathy but the staining characteristics are different (DM nephropathy is PAS and silver stain positive)
• purpura, petechiae, and ecchymoses following minor trauma ("pinch purpura")
• Appearance of periorbital purpura following a Valsalva maneuver or dependent positioning of the head.(Racoon eyes)
• Macroglossia (picture 16), waxy papules and plaques, enlarged shoulder pads, bullous lesions, and sclerodermatous changes in the skin may also be seen. (UpToDate)
• AL amyloidosis is Associated with plasma cell dyscrasia (multiple myeloma, waldenstrom macroglobulinemia)

Symptoms and signs

The symptoms and signs of AL and AA cannot reliably be distinguished. - Harrison's

• Amyloid nephropathy:
  • Heavy proteinuria (70%) - nephrotic syndrome (mild to massive proteinuria)
  • with bland sediment.
  • normal to moderately elevated S. creatinine.
• oedema
• Cardiomyopathy and heart failure (60%) - thickening of interventricular septum is present / MI due to accumulation of amyloid in coronaries.
• Neuropathies - carpal tunnel
  • mixed sensory and motor peripheral neuropathy is a prominent feature in AL amyloidosis.
    • (Symptoms of numbness, paresthesia, and pain are frequent)
• Amyloid infiltration of muscles - macroglossia with scalloping and shoulder pad sign. (also enlarged deltoids)
• Coagulopathy - possibly due to factor X binding of coagulation factors to amyloid.
• GI involvement: gastroparesis, constipation, bacterial overgrowth, malabsorption, and intestinal pseudo-obstruction resulting from *dysmotility
  • Raised ALP.

• AA amyloid is derived from a serum precursor called serum amyloid associated protein. (SAA protein).
• It is made in the liver under the stimulation of IL-1, and IL-6.

Seen in Chronic inflammatory disorders include rheumatoid arthritis, inflammatory bowel disease and untreated familial Mediterranean fever.
AA amyloidosis may complicate chronic diseases in which there is ongoing or recurring inflammation, such as rheumatoid arthritis (RA), spondyloarthritis, or inflammatory bowel disease; chronic infections.

• Similar to AL (but cardiomyopathy and neuropathy is rare)
• GI involvement: similar to AA amyloidosis

• Haemophillus influenzae can cause meningitis in babies and older adults.

• Newborns: Group B Streptococcus, S. pneumoniae, L. monocytogenes, E. coli
• Babies and young children: S. pneumoniae, N. meningitidis, H. influenzae, group B Streptococcus, M. tuberculosis
• Teens and young adults: N. meningitidis, S. pneumoniae
• Older adults: S. pneumoniae, N. meningitidis, H. influenzae, group B Streptococcus, L. monocytogenes
  Source

Paraproteinemias

• Neuropathy - POEMS Syndrome (polyneuropathy, organomegaly, endocrinopathy, M proteins and Skin disease)
  Therefore, POEMS is a paraproteinaemic neuropathy.
  P - demyelinating polyneuropathy.

Presents as a length dependent, axonal, sensorimotor neuropathy. Mild distal weakness and loss of some or all sensory modalities. Peripheral neuropathy may precede the diagnosis of the underlying condition by years. Source

• IgM paraproteins can also cause neuropathy - (anti-MAG)

| ⭐Asthma | Emphysema |

⭐The process of carbon monoxide (CO) uptake can be simplified into two components: membrane conductance (DM) and reactive conductance, the chemical reaction between CO and hemoglobin. DM reflects the properties of diffusion across the alveolar capillary interface. Uptake of CO by hemoglobin depends on the reaction rate (R) and the pulmonary capillary blood volume (Vc). The two components occur in series and when conductances occur in series, they are added as reciprocals. This relationship can be expressed as: